LCSB_PURLI
ID LCSB_PURLI Reviewed; 2507 AA.
AC A0A179H2I8;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 07-SEP-2016, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Highly reducing polyketide synthase lcsB {ECO:0000303|PubMed:27416025};
DE Short=HR-PKS lcsB {ECO:0000305|PubMed:27416025};
DE EC=2.3.1.- {ECO:0000305|PubMed:27416025};
DE AltName: Full=Leucinostatins biosynthesis cluster protein B {ECO:0000303|PubMed:27416025};
GN Name=lcsB {ECO:0000303|PubMed:27416025}; ORFNames=VFPBJ_02527;
OS Purpureocillium lilacinum (Paecilomyces lilacinus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Ophiocordycipitaceae; Purpureocillium.
OX NCBI_TaxID=33203;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], IDENTIFICATION, FUNCTION,
RP DOMAIN, INDUCTION, AND PATHWAY.
RC STRAIN=PLBJ-1;
RX PubMed=27416025; DOI=10.1371/journal.ppat.1005685;
RA Wang G., Liu Z., Lin R., Li E., Mao Z., Ling J., Yang Y., Yin W.B., Xie B.;
RT "Biosynthesis of antibiotic leucinostatins in bio-control fungus
RT Purpureocillium lilacinum and their inhibition on phytophthora revealed by
RT genome mining.";
RL PLoS Pathog. 12:E1005685-E1005685(2016).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the lipopeptide antibiotics
CC leucinostatins that show extensive biological activities, including
CC antimalarial, antiviral, antibacterial, antifungal, and antitumor
CC activities, as well as phytotoxic (PubMed:27416025). Leucinostatin A
CC contains nine amino acid residues, including the unusual amino acid 4-
CC methyl-L-proline (MePro), 2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid
CC (AHyMeOA), 3-hydroxyleucine (HyLeu), alpha-aminoisobutyric acid (AIB),
CC beta-Ala, a 4-methylhex-2-enoic acid at the N-terminus as well as a
CC N1,N1-dimethylpropane-1,2-diamine (DPD) at the C-terminus (Probable).
CC The biosynthesis of leucinostatins is probably initiated with the
CC assembly of 4-methylhex-2-enoic acid by a reducing PKS. Two reducing
CC polyketide synthases, lcsB and lcsC, have been identified in the
CC cluster and it is not clear which is the one that assembles 4-
CC methylhex-2-enoic acid since both contain KS, AT, DH, cMT, ER, KR and
CC ACP domains (Probable). The polyketide residue might be transferred to
CC the NRPS lcsA, mediated by two additional enzymes, the acyl-CoA ligase
CC lcsD and the thioesterase lcsE. The linear polyketide carboxylic acid,
CC which is released from PKS, is converted to a CoA thioester by lcsD,
CC and then lcsE hydrolyzes the thiol bond and shuttles the polyketide
CC intermediate to lcsA (Probable). The C domain of the first module
CC catalyzed the condensation of 4-methylhex-2-enoic acid and MePro
CC carried by domain A1, followed by successive condensations of nine
CC amino acids to trigger the elongation of the linear peptide. A5 and A6
CC domains of lcsA are proposed to incorporate leucine, A2 AHyMeOA, and A3
CC incorporates HyLeu. A4, A7 and A8 incorporate AIB (Probable). The
CC AHyMeOA in leucinostatin A activated by the A2 might be produced by the
CC second PKS (lcsB or lcsC) present within the cluster (Probable). The
CC MePro is probably produced via leucine cyclization and may originate
CC from a separate pathway, independent of the cluster. Another
CC nonproteinogenic amino acid, beta-Ala, could be produced by an aspartic
CC acid decarboxylase also localized outside of the cluster. Two
CC candidates are VFPBJ_01400 and VFPBJ_10476 (Probable). The final
CC peptide scaffold may be released by the NAD(P)H-dependent thioester
CC reductase (TE) at the C-terminal region of lcsA (Probable).
CC Transamination of the lcsA product by the transaminase lcsP may produce
CC DPD at the C-terminus (Probable). Further hydroxylation steps performed
CC alternatively by the cytochrome P450 monooxygenases lcsI, lcsK andr
CC lcsN then yield the non-methylated leucinostatins precursor. It is also
CC possible that leucines can be hydroxylated prior to their incorporation
CC into the peptide (Probable). Varying extents of methylation then lead
CC to the formation of leucinostatins A and B (Probable).
CC {ECO:0000269|PubMed:27416025, ECO:0000305|PubMed:27416025}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:27416025}.
CC -!- INDUCTION: Expression is positively regulated by the leucinostatins
CC biosynthesis cluster-specific transcription regulator lcsF.
CC {ECO:0000269|PubMed:27416025}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:27416025}.
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DR EMBL; LSBH01000002; OAQ83760.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A179H2I8; -.
DR SMR; A0A179H2I8; -.
DR EnsemblFungi; OAQ83760; OAQ83760; VFPBJ_02527.
DR Proteomes; UP000078240; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 2.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 2.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 2: Evidence at transcript level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2507
FT /note="Highly reducing polyketide synthase lcsB"
FT /id="PRO_0000446600"
FT DOMAIN 2425..2503
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:27416025"
FT REGION 5..396
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27416025"
FT REGION 399..501
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 581..900
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27416025"
FT REGION 953..1232
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27416025"
FT REGION 1402..1570
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27416025"
FT REGION 1793..2105
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27416025"
FT REGION 2130..2303
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:27416025"
FT COMPBIAS 400..456
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 467..492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2463
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2507 AA; 273604 MW; 71B8B478122EB585 CRC64;
MAEPIAVVGM AMRLPGNVRN GEEFWQLLVE KRNGLCDVPQ DRYNVNGFHD PSGKPSTFRM
NKGYFLQDVD IAQFDTSFFS LSKAELERLD PQQRQLLEVA YECMEDAGAT SWRGSNTGCY
VGVFGDDWQD LNAKETLHKG GYRVTGYDDF VLGNRISYEF DLHGPSMTVK TGWLIFSPTM
TLALSDQGVL SPSGICKTFD ATADGYGRGE AVNAIYIKRL SQAIEDGDSI RAIIRGTSVN
CDGRTQAMLT PSPTAQEALI RRAYEQAGIQ DMSRTAMVEC HGTGTSVGDP LEATAVANCF
GDKGIYITSV KPNVGHSEGA AGLTSLIKAI LAIEHRQIPP NIFFESPNPA IPFSKCKLRV
PVKTEEWPDA RAERVSVNSF GIGGVNAHVI VESLREYQNH DRGLSNGSTT SSSPAGDMTP
TDSDGFEDVG SSESSTVDEF ANSDGVHSNG HQDVDGSAES KASDAKLESN DTPQSRSTPS
NGDQTSHTVG RRNGYSGDDV EFPERPHLLL FSATSEPALK DTVKTYQEFL PTSHISLKDV
AYTLALRRDH KPHRAFAIAG NKSSIELSQL ETVKTPARIA WVFTGQGAQW PEMGAELIDT
NPVFQATIRG LDAFLAGLPS PPPWTIESEL RKTAGDSRVQ KAEFGHPLSI AVQIGLIDVL
KSWGIKPDLV LGHSSGEMAA AYASGSITAK AAMAAATFRG TTSTSGTAEK RGSMAAIGLG
AHEMAPYMEP GVVVACENSQ CSVTISGDSE QVEKVVQNVK TQREGVLARF LRVEKAFHSH
HMLEYGPLYE EHLQPFVSST SPLIPFYSSV TGKRLSGDGC LGPAYWRRNM ESPVLFNTAL
RSAMTAYEGR LVLIEIGPHP ALKGPIGQIL RDMGRSADVH VGTLQRDKGC DESLLQLAGK
LFQQDVNVDF SHVLLPSGRH VANLPRYPWK RDNSHWAESR MTREWRFREH APHELLGSRV
TEISNEPCWR TKLALEDVSW LSGHEVGGQV VFPGAGYISM VGEAIRQLHE ELAYSLKNVS
IKAGLVLEHG KTVEIVTSLS PVATDSSDEA SWYTFSISSY DGTKWVKHCV GEARASVDKA
AQLSVQSPKG YARTVDANEW YNILNRVGFN YTGLFRGLGS ITAAPGDNRA AASVPSLSQA
GKFAMHPAVM DQCFQLFTVS AYGGLGRNCK NIAVPTFIEE IIVRPTAHDL RVGATIHTLE
RGSFVGDLVA EQAGELQLSL KGFKASALTR SDDEDESLPL ITRFEWRPHA HFVSLADYLH
PRTHIPREWP LFEEMMLLCA IDHLETIKLT GETQPHLRKF FSWMQGQVDK YRSGRNLFVA
NDRGLLELTK AQRLGRIAEI AADGEKSQYP AFCIAIHRLF QTAESIFSGE THPLHVLMKD
DVLTEFYAVG DELNYATALR VLGHTNPRLR ILEVGAGTGG TTVKVLKALT SSTGERLYST
YTYTDISAGF MASAKERFSE VEGLQYATLD ISQDPSEQGY LEGSYDLIIG SNVIHATPNL
NVSLSHLRRL LSPGGKLFLQ ELCPDAKYVN YVMGFLPGWW LGDGDNRPDE PYISADRWAK
EMVAAGFAEP EAMVIDGITP YQQSAGIIAS PACETSKPLA VSLLSHSMDG AYVAEAKRVL
EDLGVAVDVV TFGQPLPSHD VVSLLDLQAS TVHDLTEPSF KTLVAQLQAL DLDAKVIWAT
RSAQVACTDP RTAMSLGLTR TARSELSVKL FTVEIDDKTN HLAASKCLVD ILMRRHSPQL
DAESMDPDWE YAVVDGQILV PRMHWQTMAA AFERTNGDDS RPTEKHLSVK TPGLLHTMGW
SQSERAPLEH GQVTVQTRAI GLNFRDVLIA LGVLDNSTRE IGLEGSGVVT EVGPGVEKLQ
VGDRVMYMSS GCFTTHITLS QTLCVKLDDG LTFEQGAALP CVYATAAMAL VDKANLQPGQ
TILIHSACGG VGLAAIQIAQ MLGGEVYCTV GNEDKVRYLM DNHNIPRHRI FNSRDTSFLR
DVMAVTDNRG VDVVLNSLSG ELLHASWRCV AEFGTMIEIG KRDFRRRAKL SMEAFEANRT
FVGLDLWQVS QVRPEQVARL LERCIKWMQA GSIKPGVIAR VWDAEQVQDA FRFMQGGRHI
GKIIVKMPQD SSSLESTKER PSPSLRHDRS YLLVGGLGGL GRAIATWMAE NGARHLIFLS
RSARQGPQLA SFVEELAAQG CEVQLVAGSV SCPDDVKRAV DGASKPIAGV MNLSMVLRDI
SLSDMTFADW TTAVAPKVQG TWNLHEAITS ELDFFILCSS YSGIVGQWGQ ANYAAANTFL
DAFVQYRHHK GLAASVIDIG VMGEVGFVSK NKDILGLFQK SGMRILKEQD LLDATNLAIQ
RSKPSRAQVS DGCFDSPGQI LLGLVTSVPI ASPNNRVVWK NDIRMSIYHN INGGKDSASS
ATAELDDITT LLKSAASDPS VLQDEESTVI IATAIASALA NFLIKEEGSI KVEDSPEHAG
LDSLVAMELR NWIRQRFGVD TTVMTIVQST SIMSLGDYIR TALVKRS
